@misc{oai:repo.qst.go.jp:00071083,
 author = {Kokuryo, Daisuke and Kano, Mitsunobu and Nishiyama, Nobuhiro and Saga, Tsuneo and Aoki, Ichio and et.al and 國領 大介 and 狩野  光伸 and 佐賀 恒夫 and 青木 伊知男},
 month = {Apr},
 note = {Introduction The detection of early-stage tumors, especially in the metastatic case, is important for improving treatment efficacy and prolonging patient survival.
Super paramagnetic iron-oxide (SPIO) nanoparticles are a highly sensitive MRI contrast agent and have the potential to be a powerful tool for a wide range of clinical
and pre-clinical cancer studies.1 However, after intravenous administration conventional SPIO nanoparticles (eg ferucarbotran) in the bloodstream are rapidly captured
by the reticuloendothelial system (RES), predominantly in the liver. Therefore, to avoid recognition by the RES and effectively target tumour tissue, it is necessary to
equip the SPIO nanoparticles with a "stealth" capability. Previously, it has been reported that polyion complex vesicles (Nano-PICsomes), which are composed of
biocompatible poly(ethylene glycol) (PEG) and poly(amino acid)s, can be easily engineered for size and are capable of prolonged circulation in the bloodstream.2, 3 In
this paper, a novel MR and fluorescence contrast nanocarrier (named "SPIO-Cy5-PICsome"), that is specific for targeted tumor imaging and is based on the
encapsulation of FDA-approved SPIO nanoparticles inside Nano-PICsomes, was synthesized and evaluated in vitro and
in vivo for its ability to detect small tumors with high-field MRI.
Materials and Methods The SPIO-Cy5-PICsomes were composed of ferucarbotran (Resovist®, Fujifilm RI Pharma)
and two oppositely charged block copolymers: block-aniomer, fluorescence (Cy5)-labeled PEG-b-poly(α,β-aspartic
acid) (Cy5-PEG-PAsp) and homo-catiomer, poly([5-aminopentyl]-α,β-aspartamide) (Homo-P(Asp-AP)) (Figure 1). A
solution of Cy5-PEG-PAsp and ferucarbotran was prepared and then mixed with the Homo-P(Asp-AP) solution in an
equal unit ratio of charged polymers, and stirred with a vortex mixer. The SPIO-Cy5-PICsome solution was then added
to the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) solution for cross-linking. The size of the
SPIO-Cy5-PICsomes was controlled to be around 100 nm., ISMRM 21th Annual Meeting and Exhibition},
 title = {SPIO-loaded unilamellar polyion complex vesicles (SPIO-Cy5-PICsomes) as a high relaxivity contrast agent for tumor},
 year = {2013}
}